Variant 4-2988772-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182982.3(GRK4):c.194G>T(p.Arg65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,609,242 control chromosomes in the GnomAD database, including 99,042 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 11749 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87293 hom. )

Consequence

GRK4
NM_182982.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.34

Variant links:

Genes affected

GRK4 (HGNC:4543): (G protein-coupled receptor kinase 4) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GRK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.7048926E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK4	NM_182982.3 linkuse as main transcript	c.194G>T	p.Arg65Leu	missense_variant	3/16	ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9 linkuse as main transcript	c.194G>T	p.Arg65Leu	missense_variant	3/16	1	NM_182982.3	ENSP00000381129	P1	P32298-1
GRK4	ENST00000345167.10 linkuse as main transcript	c.98G>T	p.Arg33Leu	missense_variant	2/15	1		ENSP00000264764		P32298-2
GRK4	ENST00000504933.1 linkuse as main transcript	c.194G>T	p.Arg65Leu	missense_variant	3/15	1		ENSP00000427445		P32298-4
GRK4	ENST00000398051.8 linkuse as main transcript	c.98G>T	p.Arg33Leu	missense_variant	2/14	1		ENSP00000381128		P32298-3

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57778

AN:

151888

Hom.:

11726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.0916

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.322

AC:

81000

AN:

251300

Hom.:

14383

AF XY:

0.315

AC XY:

42808

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.303

Gnomad ASJ exome

AF:

0.293

Gnomad EAS exome

AF:

0.0879

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.339

AC:

493810

AN:

1457236

Hom.:

87293

Cov.:

AF XY:

0.335

AC XY:

242584

AN XY:

725060

show subpopulations

Gnomad4 AFR exome

AF:

0.504

Gnomad4 AMR exome

AF:

0.302

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.0960

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.381

AC:

57850

AN:

152006

Hom.:

11749

Cov.:

AF XY:

0.378

AC XY:

28089

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.0915

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.453

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.347

Hom.:

24609

Bravo

AF:

0.376

TwinsUK

AF:

0.339

AC:

1256

ALSPAC

AF:

0.348

AC:

1340

ESP6500AA

AF:

0.492

AC:

2167

ESP6500EA

AF:

0.359

AC:

3086

ExAC

AF:

0.326

AC:

39524

Asia WGS

AF:

0.189

AC:

657

AN:

3478

EpiCase

AF:

0.357

EpiControl

AF:

0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.065

.;T;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.00047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

.;N;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

3.3

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.30

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.17

MPC

0.073

ClinPred

0.021

GERP RS

5.6

Varity_R

0.12

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over